Process of recovering an ascorbic acid compound



Patented June 29, 1948 PRUEESS OF BLEEOVERING AN ASCORBIC AGED COMPOUND Henry H. Bassford, Jr., Elizabeth, N. 3., assignor io'Merck & CU. Inc, Rahway, N. J., a corporatime of New Jersey No Drawing. Application June 15, 1945, Serial No. 599,744

11 (Jlaims. t

This invention relates generally to processes for preparing li-asco rbic acid and related compounds, and particularly to improvements in processes for obtaining such camper-nods from 2-l 'eto-1-gulonic acid, itsanalogues, and derivativesthereof.

It is known that rearrangement of Z-kcto-lguloni'c acid. its analogues, and derivatives thereof effected by the action oi aqueous hydrohalic acids, e. tor concentrated or dilute, to ionm. lascorbicand its analogues. The rearrangelmcnt product is then recovered from the acid solution by crystallization followed by vacuum cncentration of the mother liquors.

Concentrated aqueous hydroha'lic' acid, for example, concentrated hydrochloric acid, is prefe ably employed in this rearrangement it gives a high degree of conversion to l-ascorbic acid or the like, and further because it is possible to recover a substantial portion of the l-ascorbic acid produced as a crude crystalline product by direct crystallization from the concentrated acid, rearrangement mixture. After thus recovering a first crop of crude crystalline product, however, rec0vcry of additional product from the mother liquors is difiicult to carry out technically, and concentration of the mother liquors is usually accompanied by destruction of about half of the product originally present in the mother liquors. There are statements in the literature to the effect that l ascorbic acid is stable in concentrated hydrochloric acid. Experiments have shown, however, that l-asco rbic acid actually decomposes in concentrated hydrochloric acid according to a first order reaction and that the half life at 70 C. is about five hours. The high percentage of Lascorbic acid or related product which is retained in the another liquors, coupled with the inherent loss during concentration of the mother liquors, thus Iimitsthe commercial yield of l-ascorbic acid or its analogues from 2-l et0-l.-gul0ni-c acid, its ana logues, and derivatives thereof, by the concentrated hydrohalic acid method to about 65-70 of theory.

When dilute hydrohalic acid is used in the rearrangement the conversion to rearranged prodnot is considerably lower than with concentrated acid. Recovery of rearranged product then requires concentration of rearrangement solutionfollowed by crystallization and concentration of mother liquors as previously described, and thus results in considerable loss of product by decomposition. It has been proposed to neutralize at least part of the hydrohalic acid prior to concen- 2 same time new losses are introduced in separating the inorganic salt formed in neutralization.

It is now discovered, according to the present invention, that it is. possible to separate hydrohalic acids almost quantitatively from aqueous hydrohalic acid solutions of l-ascorbic acid and the like without decomposition of the vitamin, and. to produce essentially colorless aqueous solutions of the vitamin substantially free of inorganic components, by treating such hydrohalic acid solution with a basic lead or silver compound to precipitate the hydrohalic acid as insoluble lead or silver halide, filtering of! the insoluble halide; and whenhydrohalic" acid is removed as lead halide, precipitating the traces of soluble lead remaining in the filtrate with hydrogen sulfide gas, and filtering ofi the-sulfide precipitate. Basic'compounds which are suitable for this process include lead oxide, lead hydroxide, lead carbonate, silver oxide, silver carbonate, and the like.

Regarded in certain of its broader aspects the novel process, according to this invention, comprises treating a solution of an ascorbic acid compound of the class consisting of l-ascorbic acid and analogues thereof in aqueous hydrohalic acid, with asubstance of the class consisting of basic lead and silver compounds, filtering off the insoluble halide thus formed and recovering an aqueous solution of the ascorbic acid compound essentialy free of hydrohalic acid. Traces of lead remaining in solution after filtering oil the lead halide are removed by treating the filtrate with lriydrogen sulfide gas and filtering on the lead sulfide precipitate thus formed.

It will be noted that this process differs from conventional neutralization procedures where hydrohalic acid is neutralized with sodium hydroxide, sodium carbonate, or the like in that the hydrohalic acid is treated with an insoluble basic lead or silver compound to form an insoluble halide. The hydrohalic acid is thereby completely removed from solution without the substitution of undesired soluble inorganic components in the solution.

It was hardly to be expected that this process would provide a means for quantitatively recovering l-ascorbic acid in aqueous solution from an aqueous hydrohalic acid solution of l-ascorbic acid as it is reported in the literature that the lead ion can be used to precipitate ascorbic acid from aqueous solution as lead ascorbate. It is found, however, that in the process here disclosed that no appreciable quantity of lead ascorbate precipitates.

If the rearrangement mixture contains a high adsorption of l-ascorbic acid by the lead or silver halide precipitate is reducedto a minimum. It

will be noted in this connection that halide prev; cipitates are crystalline, free-filtering, and readily washed free of l-ascorbic acid. f

The diluted hydrohalic acid solution may first be decolorized by treatin with a small amount of activated charcoal and filtering. Anamount of basic lead Or silver compound equivalent to the hydrohalic acid present is added to the solution with stirring and the temperature is held,

with cooling if necessary, below about 45 C. Maximum recovery of the ascorbic acid compound isattained when the stoichiometric quantity of the basic compound is employed. This is apparently-due tothe fact that leader silver ions'in solution tend to catalyze decomposition of the ascorbic acid compound. However,- as it is difficult to determine the exact stoichiometric quantity of basic compound required and further, as both the basic compound and the .halide formed in the reaction are substantially insoluble,-it is found that in commercial application a substantialexcess of the basic compound, can be used without serious, reduction in'the amount of ascorbic acid compound recovered. Neutralization of the hydrohalicacid with lead or silver carbonate is particularly advantageous as no heat is evolved in" the reaction and cooling is unnecessary.- The neutralization proceeds at a gradual and relatively uniform rate even when all-of the carbonate is added at once and no care is neededto-avoid excessiveioaming due to carbon dioxide liberated. i

Theiprecipitated'lead or silver halide is then filtered off, preferably at about room temperature, and the filter cake is washedrwith asmall amount of coldwaten- In the case of lead halide the filtrate and washings-contain asmall amount of soluble lead halide from which-the. leadjion isquantitatively removed bypassing hydrogen sulfide gas through the solution, preferably ,in the presence of a'small amountof activated charcoal, and filtering ofi the lead sulfideprecipitate: Inthe :case of silverhalides, which.- are almost completely insoluble, the'filtrate and washings are completely free of hydrohalic acid and essentially free of silver ions, andthe treatment with hydrogen sulfide is therefore notessential.- The-resulting aqueous-solution of l-ascorbic acidor ananalogue thereof-is of good color and contains as high as 98% of the l-ascorbic acid originally present in -the solution before treat.- mentwith the basic lead or silver compound. The productis readily recovered from the solution by known methods as, for example, by vacuum concentration and crystallization.

An-important practical aspect of the invention is'the simple and economical natureof the process in commercial application. While the basic lead and. silver compounds arerelatively. costly reagents, they; can bereadily regenerated from the halide compounds.v The lead compoundsin particular can be easily and inexpensively regenerated by treatment of thehalides with ammo-v nium hydroxide, sodium hydroxide, sodium car.- bonate and the like. It is more difficult to re- 4 cover lead from the sulfide but the amount converted to sulfide is very small.

Throughout the specification reference has been made to rearrangement of 2-keto-1-gulonic acid, its analogues, and derivatives thereof to 1- ascorbictacid and its analogues. By the term fana'loguesi; is. meant 2 01 3' keto hexonic acids, the corresponding rearranged products which are other ascorbic acids; 2 or 3 keto hexamethylonic acids, the corresponding rearranged products whicharedesoxy ascorbic acids, and the like. By the term derivatives is meant compounds of the-type of diacetone 2-keto-1-gulonic acid which are readily hydrolyzed by acid to 2-keto-1 gulonic acid or arr analogue thereof.

vj/Vhilethe process of the present invention can be .used to remove any hydrohalic acid from an aqueous solution containing l-ascorbic acid and the like,"it-will be understood that from a practical standpoint hydrochloric acid, hydrobromic acid,-: orhydriodie acid, in the ,order mentioned, are the hydrohalic acids most likely to be present in rearrangement (mixtures containing,- l-ascorbic acid andthe like. The basic lead compounds and the; leadhalides referred to are divalent-lead or plumbous compounds. 1

The .f-ollowingygexamples illustrate methods of carrying out therpresent inventionbutit is to be understood that theseexainples arev given by way-of illustration-.andnot, of limitation.

. man I About 35 g. of diacetone z lretml -gulonic acid monohydrate is dissolved inf 117.5 g. i of concentrated aqueous hydrochloric acidan'd the solution is heatedandstirr e'd for one hour at 'l0C. The resulting solution is cooled. and. the temperature inept at. about 01!}. fory' llOjj-lg hours to'crystallizje outla first, crop orcmde' l-ascorbic acid. The crystals are filtered off, washed,, and dried yielding. about .113 g. of {light gray l--ascorbic acid assaying 95% pure, a recovery of ]of theory. Thefmother liquor and washings, aref'co'mbined, diluted with anlequal'volumeiof wateiflfand decolorized by, stirring for, to hour at room temperature with 1 g. of activated charcoal and filtering." This solutionfcontainsby assay '8.5 g. of Lascorbic acidand 5.5 g..of

About.,l8.fg.. for. litharge' 1(plunibous (oxide); which is slightly in excess of that equivalent to the I-ICLis added to 'thejsolution and stirred for 15, minutes whilekeeping theftemperature at about 40 o. a The mix'ture is then: cooled to about 20 op ns the precipitated lead chloride is n1 tered off and washed with 2X 15 cc. of cold water. About 0.; g.,;of activated charcoal is added to the filtrate and. hydrogen 'sulfide gas isbubbled'in with stirring for a: sufficient time to precipitate the lead remainingin' the: filtrate as lead: sulfide. The lead',sulfide-charcoal is filtered ofi and washed with, 3 10f c, of water, ,The filtrate contains by assay about 0.1% of HCl and about 7.6 g. of l-ascorbic acid (approximately recovery fromtheorig'inal mother liquor) Ihe filt'rateis. concentrated under vacuum and at a temperature of 4 0- -5 Q C, to'sm'all volume'and l-ascorbic acidfis crystallizedout and recovered by filtration, washing and drying. -l urther concentration of mother liquor and washings yields additional crystalline product, and a total of approximatelyfifi' g. of nearly white lascor'bicacid, assaying about 98% pure, isthus obtainedf The overall. yield of crude l-ascorbic' acid from the diacet'oneZ-keto-l guloniclaoid monohydrate pure,

ed, with vigorous stirring, with 100 cc. of a solution containing 19 g, of concentrated aqueous ammonium hydroxide. The resulting slurry is cooled to about room temperature, filtered, washed free of ammonium chloride and dried. The lead hydroxide thus obtained contains by assay 16.8

g. of lead oxide.

Example II The procedure of Example I is repeated using a quantity of litharge which is the stoichiometric equivalent of the EC] in the rearrangement solution, and washing the lead chloride precipitate after filtration with 3x20 cc, of cold water. The filtrate and washings thus obtained contain by assay about 8.3 g. of 1-ascorbic acid (approximately 98% recovery from the original mother liquor).

Concentration and crystallization of the filtrate and washings yields about 7.4 g. of almost white crystalline 1-ascorbic acid assaying about 98% The overall yield of crude l-ascorbic acid from -diacetone-2-keto-l-gulonic acid monohydrate is therefore 18.7 g. containing by assay 17.3 g. of pure l-ascorbic acid, about 82% of theory.

Example III About 35 g. of diacetone-2-keto-d-gluconic acid is dissolved in 35 g. of 40% hydrobromic acid. The solution is heated with stirring at 70 C. for one hour to efiect rearrangement, and the resulting solution is diluted with an equal volume of water, treated with 1 g. of activated charcoal, and filtered to remove tars and colored impurities. About 22 g. of lead oxide is added to the filtrate and stirred for one hour at about 40 C. to convert hy-drobromic acid to lead bromide. The solution is then cooled to roomtemperature and the lead bromide filtered oil and washed. About 0.5 g. of activated charcoal is added to the combined filtrate and washings and hydrogen sulfide gas is bubbled in to precipitate the small amount of lead present as lead sulfide, which is filtered oil. The filtrate is then given a further treatment with activated charcoal and hydrogen sulthis to insure complete removal of lead ion from the solution, The lead free filtrate is essentially free of h'ydrobromic acid and contains, by assay, 18.0 g. of d-araboascorbic acid.

The solution is concentrated under vacuum at about 50 C. to a volume of about 37 00., treated with 1 g. of activated charcoal at 60 C., filtered, and cooled to about C. The solution is allowed to stand for 8-10 hours at 0 C. to crystallize out a first crop of d-araboascorbic acid which is filtered off and washed. 10.2 g. of d-araboascorbic acid assaying about 99.8% pure is thus obtained; 48.2% of theory based upon the original dia'cetone-Z-keto-d-gluconic acid. By further concentration of the combined mother liquor and washlugs and crystallization about 7.6 g. of crude daraboascorbic acid, assaying 95% pure, is obtained. The combined yield of pure and crude product represents an overall yield of 82.5% of theory.

Example IV '75 cc. of an aqueous hydrochloric acid-l-ascorbic acid solution obtained as mother liquor and washings after crystallizing a first crop of crude l-ascorbic acid from a rearrangement solution is diluted to about 125 cc. with water. The

dilute solution ls-determined by assay to contain about 5.2 g, of l-ascorbic acid and 4.3 g. of HCl. The solution is treated with about 1 g. of activated charcoal and filtered to remove colored impurities About 15.7 g. of lead carbonate (approximately the stoich'iometric equivalent of the HCl) is added and the mixture is stirred for about an hour. The lead chloride precipitate is then filtered off and washed, The combined filtrate and washings are concentrated to small volume and crystallized in the manner described in Example I and a total yield of 5.0 g. of l-ascorbic acid assaying 96% pure is obtained, representing a recovery of approximately 92.3% based upon the amount of l-ascorbic acid in the original mother liquor and washings.

The lead chloride is suspended in about 300 cc. of water and heated to boiling with strong agitation. The calculated amount of soda ash equivalent to the lead chloride is added slowly to theagitated mixture being careful to avoid excessive foaming. Additional soda ash is added, if necessary, to make the mixture definitely alkaline to phenol-phthaline. Boiling is continued for about three hours after all the soad ash is added and the mixture is then allowed to cool and settle. The precipitated lead carbonate is filtered oil and washed until the remainin chloride is negligible.

The lead carbonate thus recovered is suitable for use in treatment of additional aqueous, hydrochloric-l-ascorbic acid solution.

Example V About 180 cc. of mother liquor and washings obtained after crystallizing a first crop of crude l-ascorbic acid from a hydrochloric acid rearrangement solution is found by assay to contain approximately 12.8 g. of l-ascorbic acid and 8.3 g. of 1101. This solution is diluted with about 1 'cc, of water and treated with about 1.5 g. of activated charcoal to remove colored impurities. Approximately 263 g. of silver oxide is then added and the mixture is stirred for about one-half hour during which time the chloride ion is removed from solution as silver chloride. The silver chloride is filtered off and the filter cake is washed with about 3x15 cc, of water. The aqueous solution thus obtained is essentially free of H01 and contains by assay 12.4 g. of 1-ascorbic acid, or 97% of that originally present in the mother liquor.

Modifications may be made in carrying out the present invention without departing from the spirit and scope thereof, and the invention is to be limited only by the appended claims.

What is claimed is:

l. The processthat comprises treating a solution of an ascorbic acid compound of the class consisting of ascorbic acids and 'desoxy ascorbic acids in aqueous hydrohalic acid, with a substance of the class consisting of insoluble basic silver and divalent lead compounds, filtering oil the insoluble halide thus formed, and recovering an aqueous solution of the ascorbic acid compound essentially free of hydrohalic acid.

2. The process that comprises treating a solution of an ascorbic acid compound of the class consisting of ascorbic acids and desoxy ascorbic acids in aqueous hydrohalic acid, with an insoluble basic divalent lead compound, filtering ofi the insoluble lead halide thus formed, and recovering an aqueous solution of the ascorbic acid compound essentially free of hydrohalic acid.

3. The process that comprises treating a solution of an ascorbic acid compound of the class consisting of ascorbic acids and desoxy ascorbic acids in aqueous hydrohalic acid, with an insoluble basic divalent lead compound,gfiltering off the insoluble lead halidethus formed, recovering an aqueous solution of theascorbic acidvcompound essentially free-of hydrohalicacid and containing a small amount of diss-olvedlead halide, andromoving the lead from said solution by treating the solution with hydrogen sulfide gas and filtering .off the insoluble lead sulfide thus-,formecl: I

1-4. The process for recovering anlascorbic acid compound of the class consisting of asconbicflacids and desoxy. ascorbic acids from a rearrangement solution comprising a compound of the class described in aqueous hydrohalic acid solution,,that comprises first reducing the concentration of the ascorbic acid compound toat least the point Where no crystallization thereof will occur at room temperature, treating the solution thus obtained with a: substance of the ,class consisting of insoluble basic silver and divalent lead compounds, filter,- ing off the insoluble halide. thus formed, and recoveringan aqueoussolution of the ascorbic acid compound essentially free of hydrohalic acid. I 5..The 'process for removing hydrohalic. acid from an aqueous hydrohalic acid-solution ofan ascorbic acidcompound lof-the class consisting of ascorbic acids and 'desoxyascorbic, acids, that comprises treating said solution with an amount of a t substancev of the class consistingtof insoluble basic silver and divalent lead compounds which is substantially equivalent .stoichiometrically' to the hydrohalic acid in said solution, and filtering off the insoluble halide thus formed.

,6; The process that comprises treating asolution of l-ascorbic acid "in. aqueous-,hydrohalic acid, with a substance of the class consisting of insoluble basic silverand divalent leads compounds, filtering :ofi the: insoluble phalide "thus formed, and recovering anaqueous solution of l-ascorbic acid. essentiallytiree of hydrohalic {ZrThe process that comprises treating asolution of d-araboascorbic acid in aqueoushydrohalic acid, with a substance of the class'consisting of insoluble basic silver and divalent --lead compounds, filtering off the insoluble halide thus formed, andrecovering an aqueous solutionaof d-araboascorbic acid, essentially free of hydrohalicacid.1 iv e M 8. The process that comprises treating a solution of l-ascorbic acid in aqueous hydrohalic acid,@ vith an insoluble basic divalentllead comipound, filtering off the insoluble ,leacl halide 8 thus formed, recovering an aqueous solution of l-ascorbic acid essentiallyfree of hydrohalic acid and containing asmall amount of dissolved lead halide,- and removing the lead from said solution by treating the solution with hydrogen sulfidegas and filtering oil the insoluble lead sulfide thus formed.

. 9. The .-process that comprises treating an aqueous hydrochloric acid solution of l-ascorbic acid with plumbousoxide, filtering off the insoluble plumbous chloride thus formed,,and recovering an aqueous solutionof l-ascorbicacid essentially free of hydrochloric acid,

' 10. The process that comprises 'ftreating an aqueous hydrochloric acid solution of l-ascorbic acid with plumbous carbonate,filtering oil the insoluble plumbous chloride thus formed, and recovering an aqueous solution of l-ascorbic acid essentially fre'eof hydrochloric acid.

11. The process that comprises treating an aqueous hydrochloric acid solution of l-ascorbic acid with an amountof plumbous carbonate substantially equivalent stoichiometrically to the hydrochloric acid in said solution, filtering ofi the insoluble plumbous chloride thus formed, recovering an aqueous solution of l-ascorbic acid essentially free of hydrochloricacid and containing a smallamount of dissolved plumbous chloride, and'removing" the lead from said solution by treating the solution with hydrogen sulfide gas and filtering off the insoluble lead sulfide thus formed.' v v HENRY BASSFORD, JR.

u BEFERENCESCITED The following references are "of record in the file of this patent: V r

- UNITED STATES PATENTS Number I i l I Name Date 2,189,830 o Zimma t Feb. 13, 1940 FOREIGN PATENTS Number 1 Country Date 46 1,790 GreatBritain Feb. 24, 1937 {OTHER REFERENCES Szent-Gyorgyi-Biocheinl Jour. 22 1394 (1928). R; Rosenberg-Chemistry & Physiology of the Vitamins Interscience'Publisher's-(1924) page I-Iackhs Chemical Dictionary 3rd edit The Blakiston Co. p e 

